The overall objective of this research program is to increase our knowledge of bile acid conjugation. We intend to investigate all aspects of the enzymology of bile acid conjugation, i.e., the catalytic properties, regulatory properties, and structural aspects of both the cholyl-CoA synthetase and the cholyl-CoA:glycine/taurine N-acyltransferase(s). We should like to determine, at the level of enzyme chemistry, the basis for the evolutionary change from strict taurine-conjugating activity in non-mammals to both glycine- and taurine-conjugating activity in placental mammals. Our investigations into the biochemical basis for the wide species variations in the ratio of glycine to taurine conjugates excreted in the bile (G/T) will be continued. We will also investigate the wide variation in G/T which accompanies the development of certain mammalian species. At some point, we also hope to be able to investigate the variations in G/T associated with certain disease states, such as ileal disorders, hypothyroidism, etc. We will study the effect of various administered drugs on the bile acid-conjugating enzymes in the liver, beginning with the contraceptive steroids which are known to induce cholestasis and are suspected of depressing bile acid conjugation. Over the long term, we are seeking an understanding of why bile acids are conjugated and all the ramifications of their having been conjugated.